The major objectives of this proposal are to determine: 1) the biochemical characteristics of the proteolytic enzymes released by rabbit pulmonary alveolar macrophages which are capable of degrading types I, III, IV, and V collagen, and elastin, 2) the factors regulating the secretion of these enzymes; and 3) their possible role in several experimentally induced lung diseases. These enzymes will be purified to homogeneity from culture medium obtained from isolated alveolar macrophages. The effect of these purified enzymes on their respective substrates will be characterized with particular interest in the reaction products generated and the cleavage sites. The factors affecting the release of these enzymes in vitro by macrophages will be studied. Resident macrophages will be harvested from the lungs of normal rabbits and "activated macrophages" will be harvested from rabbits pre-treated with complete Freund's Adjuvant. These cells will be cultured in the presence of various pharmacologic agents and biologic substances and the medium assayed for degradative activity against each individual substrate. This will identify agents which may modulate the release of the matrix-degrading proteinases. The role of these enzymes in specific experimental pulmonary diseases will be investigated. Pulmonary fibrosis, granulomatous disease, and emphysema will be induced in rabbits and other laboratory animals and macrophages harvested from the diseased lungs at various time points. The in vitro release of these individual proteinases will be quantitated to determine their potential role in the pathogenesis of the induced disorder. In addition, the chemical nature of the extracellular matrix proteins will be determined biochemically and immuno-histochemically to identify any qualitative or quantitative changes in the individual components.